The primary objective of this program is the development of GC/MS methodology for the analysis of dopaminergic agonists such as apomorphine and related compounds and natural products isolated from plants exhibiting antitumor activity. Trimethylsilyl derivatives have been found to be useful for the structural analysis of hydroxylated sesquiterpenes in view of both their good GC properties and interpretable mass spectra. The trimethylsilylation of certain methylated aporphines has revealed the occurrence of an unusual demethylation process which appears highly selective and structurally dependent. This reaction is being investigated further in view of its potential value in the synthesis of aporphine analogs. A GC/MS combination using 6 ft, 2mm i.d. packed columns interfaced to the mass spectrometer via a low conductance direct transfer line, without the need for a separator or stream splitter, has been developed and is being used in this study. Transfer efficiencies on the order of 90% from the GC to the MS at the 1 microgram sample level have been determined for this system with typical standard compounds such as cholestane or methyl stearate. In related activity we have determined the mass spectrometric sensitivity of a variety of biologically signficant compounds in terms of ion current per sample quantity (coulombs/mug). The implications of these measurements to trace level detection and quantitative analysis by GC/MS have been evaluated. On the basis of the latter studies a methodology has been developed for the analysis of thyroid hormones and their precursors as their heptafluorobutyryl-methyl ester (HFB-ME) derivatives.